Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas

Leung, Po Sing; Carlsson, Per‐Ola

doi:10.1677/jme.0.0260155

Cited by 117 publications

(93 citation statements)

References 66 publications

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“…The existence of such a system makes a local production of Ang II probable, which produces its concentrations several times higher than those measured in peripheral blood. Indeed, islet blood flow seems to be suppressed by such locally produced Ang II during normal conditions [8,16]. More importantly, Ang II induced a marked and dose-dependent decrease of glucose-stimulated insulin release from isolated islets in the present study, indicating that Ang II plays an important role in regulating islet insulin secretion.…”

Section: Discussionsupporting

confidence: 55%

“…This further indicates that the inhibitory action of Ang II was mediated through the AT 1 -receptors, which were located in the beta cells of pancreatic islets. Previous studies reported that receptors for Ang II have also been identified in the animal pancreatic islets [8,32], but at least in rat, they were localised preferentially to the surface of alpha-and delta-cells [32]. In the human pancreas positive cells for AT 1 -receptor seem, however, to be distributed to those cells stained with insulin [13] although the precise localisation of the AT 1 -receptors has yet to be established.…”

Section: Discussionmentioning

confidence: 95%

“…This implies that locally produced Ang II exerts local actions from such diverse targets as the heart [5], adrenals [6] and gonads [7] to the pancreas, recently reviewed [8]. Previous studies have shown the presence of such a local system in the pancreas of various species, including the dog [9], rat [10,11], mouse [12] and human [13].…”

Section: Measurements Of (Pro)insulin and Total Protein Biosynthesismentioning

confidence: 99%

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Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

2004

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Aims/hypothesis. A local angiotensin-generating system has been found in the exocrine pancreas. This study aimed, primarily, to investigate the existence of a local angiotensin-generating system in the pancreatic islets and, secondly, to elucidate its role in regulating insulin secretion. Methods. Real-time RT-PCR and western blot were used to investigate if angiotensin-generating components are present in the mouse pancreatic islets, which are subject to regulation by islet transplantation. The localisation of AT 1 -receptors in islets was investigated by immunohistochemistry. Batch-type incubations of isolated islets were applied for studying the influence of angiotensin II on the glucose-stimulated insulin release, glucose oxidation and (pro)insulin, and total protein biosynthesis. Results. Major components, namely angiotensinogen, ACE, AT 1 -and AT 2 -receptors, were expressed in endogenous islets. AT 1 -receptors were localised to pancreatic beta cells. Exposure of the isolated islets to angiotensin II induced a dose-dependent inhibition of glucose-stimulated insulin release and inhibited (pro)insulin biosynthesis. This inhibitory action was fully preventable by pretreatment of the islets with losartan, an AT 1 -receptor antagonist. We also investigated if the expression of these components was changed after islet transplantation. Notably, a markedly increased expression of mRNA for the AT 1 -receptor was observed in islets retrieved from 4-week-old syngeneic islet transplants, a finding that was confirmed at the protein level. Conclusion/interpretation. These data indicate the existence of an islet angiotensin-generating system of potential importance in the physiological regulation of glucose-induced insulin secretion, thus diabetes mellitus. The increased expression of the AT 1 -receptor in islet transplants could have relevance to islet-graft function. [Diabetologia (2004) 47:240-248]

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 95%

Section: Measurements Of (Pro)insulin and Total Protein Biosynthesismentioning

confidence: 99%

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Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

2004

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“…An intrinsic pancreatic angiotensin-generating system was demonstrated in the canine pancreas [8,9] by localisation of mRNA and protein for AGT and Ang II receptors, and subsequent studies have identified RAS components in rat, mouse and primate pancreas [7,10,11]. The highest densities of pancreatic Ang II receptors are reported to be localised to pancreatic ducts, vascular endothelium and acinar cells [10]. Although it has recently been reported that AT 1 receptors are localised to mouse pancreatic beta cells [11], there is currently no direct evidence of AT 1 receptor expression by human islet beta cells, nor of the effect of exogenous Ang II on human islet function.…”

Section: Introductionmentioning

confidence: 99%

Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans

Ramracheya

Müller

et al. 2006

Diabetologia

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Aims/hypothesis: This study aimed to identify the expression of angiotensin II receptors in isolated human islets and beta cells and to examine the functional consequences of their activation. Materials and methods: Singlecell RT-PCR was used to identify whether human islet cells express mRNA for type 1 angiotensin II receptors (AT 1 ), and western blotting was used to determine AT 1 protein expression by human islets and MIN6 beta cells. We measured changes in intracellular calcium by microfluorimetry using Fura 2-loaded MIN6 cells and human islet cells. Dynamic insulin secretory responses were determined by RIA following perifusion of human islets and MIN6 cells. Results: Human islets expressed mRNAs for both the angiotensin precursor, angiotensinogen, and for angiotensin-converting enzyme. In addition, human and mouse beta cells expressed AT 1 . These were functionally coupled to increases in intracellular calcium, which occurred at least in part through phospholipase-C-sensitive mechanisms and calcium influx through voltage-operated calcium channels.Short-term exposure of human islets and MIN6 cells to angiotensin II caused a rapid, short-lived initiation of insulin secretion at 2 mmol/l glucose and potentiation of insulin secretion induced by glucose (at 8 and 16.7 mmol/l). Conclusions/interpretation: These data demonstrate that the AT 1 is expressed by beta cells and that angiotensin II effects a short-lived and direct stimulation of human and mouse beta cells to promote insulin secretion, most probably through elevations in intracellular calcium. Locally produced angiotensin II may be important in regulating a coordinated insulin secretory response from beta cells.

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“…Such a local pancreatic RAS plays a pivotal role in regulating the endocrine and exocrine functions of the pancreas (see review by Leung & Chappell 2003). Interestingly, the components of this local system are responsive to various physiological and pathophysiological stimuli (see review by Leung & Carlsson 2001). For example, our recent studies showed that the pancreatic RAS components were upregulated by experimental models of acute pancreatitis and chronic hypoxia .…”

Section: Introductionmentioning

confidence: 99%

The recovery of some components of the renin angiotensin system in the rat pancreas after chronic exposure to hypoxic condition

Wong

Tsai³

et al. 2003

Journal of Molecular Endocrinology

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Previous studies have shown that the expression of the major components from a local pancreatic renin-angiotensin system (RAS) was upregulated after chronic exposure to oxygen deprivation (10% oxygen). In the present study, the reversibility of expression for the pancreatic RAS affected by chronic hypoxia was investigated in the pancreas. Rats were first subject to hypoxia for one month and they were then returned to normoxic conditions for a varying period of time (1, 2, 3 and 4 weeks). The degree of recovery in the expression of RAS components was analyzed with standard curve-quantitative competitive-reverse transcription-polymerase chain reaction (SC-QC-RT-PCR), Western blot analysis and a specific assay for angiotensin-converting enzyme (ACE) activity. Results from SC-QC-RT-PCR showed that the upregulated expression of angiotensin II type 1 (AT 1 ) receptor mRNA following chronic hypoxia could be completely restored to the control level after the rats were returned to the normoxic condition for 3 weeks. The reversibility of mRNA expression for angiotensin II type 2 (AT 2 ) receptor and angiotensinogen was observed after the return to normoxic conditions for 2 and 3 weeks respectively when compared with that of their respective controls. Results from Western blot analysis further confirmed that the expression of AT 1 receptor protein was also reversible after return to normoxic conditions for 4 weeks. In addition, the activation of ACE activity returned to its normal level in a time-dependent manner. These data indicate that the upregulation of a local pancreatic RAS affected by chronic hypoxia could be recoverable. The significance of its reversibility and adaptability following chronic hypoxia may be of physiological relevance to the pancreas.

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Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas

Cited by 117 publications

References 66 publications

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

Evidence for a local angiotensin-generating system and dose-dependent inhibition of glucose-stimulated insulin release by angiotensin II in isolated pancreatic islets

Direct regulation of insulin secretion by angiotensin II in human islets of Langerhans

The recovery of some components of the renin angiotensin system in the rat pancreas after chronic exposure to hypoxic condition

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